TCLF 2018

LA JOLLA, CALIF. – In patients with relapsed peripheral T-cell lymphoma, the goal before moving to transplant is achieving complete or near-complete remission, according to Steven M. Horwitz, MD, of Memorial Sloan Kettering Cancer Center, New York.

“If you’re really trying to go to transplant, you want a complete remission or close to it. So that’s often been combination chemotherapy. But I think what we’re learning is, when some of the newer agents are combined, we’re seeing higher complete response rates. And we’re doing a better job at picking subtype specific approaches,” Dr. Horwitz said in a video interview at the annual T-cell Lymphoma Forum.

Dr. Horwitz also explored the role for reduced-intensity regimens in older patients, the use of radiation conditioning, and which new agents look most promising in peripheral T-cell lymphoma.

Dr. Horwitz had previously disclosed financial relationships with Celgene, Forty Seven, Huya Bioscience International, Infinity, Kyowa Hakko Kirin, Millennium, Seattle Genetics, and Takeda. The T-Cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization.

mschneider@frontlinemedcom.com

SOURCE: Horwitz SM. TCLF 2018.

LA JOLLA, CALIF. – In patients with relapsed peripheral T-cell lymphoma, the goal before moving to transplant is achieving complete or near-complete remission, according to Steven M. Horwitz, MD, of Memorial Sloan Kettering Cancer Center, New York.

“If you’re really trying to go to transplant, you want a complete remission or close to it. So that’s often been combination chemotherapy. But I think what we’re learning is, when some of the newer agents are combined, we’re seeing higher complete response rates. And we’re doing a better job at picking subtype specific approaches,” Dr. Horwitz said in a video interview at the annual T-cell Lymphoma Forum.

Dr. Horwitz also explored the role for reduced-intensity regimens in older patients, the use of radiation conditioning, and which new agents look most promising in peripheral T-cell lymphoma.

Dr. Horwitz had previously disclosed financial relationships with Celgene, Forty Seven, Huya Bioscience International, Infinity, Kyowa Hakko Kirin, Millennium, Seattle Genetics, and Takeda. The T-Cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization.

mschneider@frontlinemedcom.com

SOURCE: Horwitz SM. TCLF 2018.

LA JOLLA, CALIF. – In patients with relapsed peripheral T-cell lymphoma, the goal before moving to transplant is achieving complete or near-complete remission, according to Steven M. Horwitz, MD, of Memorial Sloan Kettering Cancer Center, New York.

“If you’re really trying to go to transplant, you want a complete remission or close to it. So that’s often been combination chemotherapy. But I think what we’re learning is, when some of the newer agents are combined, we’re seeing higher complete response rates. And we’re doing a better job at picking subtype specific approaches,” Dr. Horwitz said in a video interview at the annual T-cell Lymphoma Forum.

Dr. Horwitz also explored the role for reduced-intensity regimens in older patients, the use of radiation conditioning, and which new agents look most promising in peripheral T-cell lymphoma.

Dr. Horwitz had previously disclosed financial relationships with Celgene, Forty Seven, Huya Bioscience International, Infinity, Kyowa Hakko Kirin, Millennium, Seattle Genetics, and Takeda. The T-Cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization.

mschneider@frontlinemedcom.com

SOURCE: Horwitz SM. TCLF 2018.

LA JOLLA, CALIF. – When patients with peripheral T-cell lymphoma (PTCL) experience relapse, consider an allogeneic stem cell transplant or clinical trial, investigators advised.

Patients with relapsed PTCL have generally dismal outcomes, with a median progression-free survival (PFS) of 3.7 months and a median overall survival (OS) of just 6.5 months, according to one study (J Clin Oncol. 2013 Jun 1;31[16]:1970-6).

Courtesy Larry Young

She outlined her center’s approach for treating patients with relapsed or refractory PTCL, following a case presentation by Royal Marsden fellow Matthew Cross, MD.

Complex disease, multiple therapies

The patient was a 71-year-old woman who in 2007 had a diagnosis of asymptomatic stage 4A follicular lymphoma managed with observation; in 2010, she was diagnosed with a CD30-positive PTCL not otherwise specified with ongoing low-level bone marrow involvement with follicular lymphoma.

She initially was treated elsewhere with R-CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab) and had a response after four cycles; however, she had progression with new intra-abdominal nodal sites by the sixth cycle and then was started on two cycles of ESHAP (etoposide, methylprednisolone, high-dose cytarabine, and cisplatin), but she had further progression by May 2011 and opted to forgo additional treatment.

By July 2011, however, she became highly symptomatic with new pruritic rashes on her legs, abdominal pain, and distention. She was referred to the Royal Marsden Hospital, where she was eventually diagnosed with angioimmunoblastic T-cell lymphoma (AITL) with an Epstein-Barr virus–negative clonal large B-cell proliferation in her bone marrow.

She was treated with gemcitabine plus methylprednisolone and prophylactic intrathecal methotrexate and had an “excellent clinical and radiological response,” Dr. Cross said.

A subsequent bone marrow biopsy showed marked hypocellularity but no evidence of either T-cell of B-cell lymphomas.

An autologous stem cell transplant was planned, but two attempts at harvesting peripheral blood stem cells – including one with plerixafor (Mozobil) – failed, and a PET scan within 3 months showed signs of early progression.

In April 2012, the patient was started on romidepsin (Istodax) and had a 1-year remission. But in April 2013, a repeat biopsy again showed CD30-positive AITL. Based on the CD30 positivity, the patient was started on brentuximab vedotin (Adcetris) in May 2013. She was observed to have progression in inguinal nodes in January 2014; she was treated with local radiotherapy and continued on brentuximab but had further progression in June 2014. At that time, she had additional gemcitabine-based combination chemotherapy and had stable disease for 10 months.

In March 2015, she received lenalidomide for further progression but could not tolerate the drug. She died in September 2015, 5 years after diagnosis and 4.5 years after frontline therapy failed.

Therapeutic rationale

Dr. Dearden walked through the choices that she, along with Dr. Cross and their colleagues, made in treating the patient. They chose gemcitabine-based regimens for salvage therapy because of the drug’s efficacy across various forms on non-Hodgkin and Hodgkin lymphoma, she said.

However, a randomized, phase 3, noninferiority trial in the United Kingdom comparing GEM-P (gemcitabine, cisplatin, and methylprednisolone) with CHOP for first-line therapy of PTCL was halted at the interim analysis because GEM-P had not meet the primary endpoint, she said. Results of that trial have not been published to date.

“Clearly, if it’s the patients who do well, often it’s because they achieve a good enough remission to be able to proceed to some sort of consolidation therapy with autologous or allogeneic stem cell transplants, and I think auto-graft is probably accepted for the younger, fitter patients with relapsed chemo-sensitive disease,” she said.

Three-year survival rates for autologous hematopoietic stem cell transplantation range from 36% to 58% and are better than those seen with chemotherapy alone, she said.

“The problem of course is that not many patients receive the planned auto-graft, even if that’s the intention, either because of failure to respond to salvage regimen or early disease progression, which happens before the transplant is able to take place,” she said,

A reasonable alternative for patients with relapsed/refractory PTCL is allogeneic transplantation, as shown in a 2008 study.

Among 77 patients – 57 of whom had received myeloablative conditioning, 31 of whom were in complete remission, and 26 of whom had partial response at the time of transplants – the 5-year treatment-related mortality rate was 33%. However, the 5-year event-free and overall survival rates were 53% and 57%, respectively. Patients with AITL had especially good outcomes (J Clin Oncol. 2008 May 10;26[14]:2264-71).

“In an ideal world, if our patient had been a suitable candidate for an allo-transplant, it’s what we would have tried to undertake,” Dr. Dearden said.

Dr. Dearden recommended that all patients with relapsed or refractory PTCL be considered for clinical trials. For fit patients in first relapse, combination platinum-based chemotherapy followed by autologous or allogeneic transplant may be effective.

For patients not eligible for transplant or with chemotherapy-refractory disease, she recommended trying the following monotherapy approaches: pralatrexate for patients with PTCL not otherwise specified, histone deacetylase inhibitors or 5-azacytidine for AITL, brentuximab vedotin for anaplastic large cell lymphoma, and pembrolizumab for natural killer/T-cell lymphomas.

Although two lines of intensive chemotherapy had failed the case patient within 6 months of diagnosis, she still survived for 5 years with sequential monotherapies, Dr. Dearden noted.

“I use to say to her, ‘You just need to stay one drug ahead of your disease.’ And she was well, she had a very good quality of life for a period of time, and if you can deliver a treatment that is effective for a patient, it will extend their survival,” Dr. Dearden said.

The T-cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization. Dr. Dearden has consulted for MedImmune, Infinity Pharmaceuticals, Janssen, Gilead Sciences, and Roche, and has received honoraria from Janssen and Gilead. Dr. Cross reported no having no financial disclosures.

LA JOLLA, CALIF. – When patients with peripheral T-cell lymphoma (PTCL) experience relapse, consider an allogeneic stem cell transplant or clinical trial, investigators advised.

Patients with relapsed PTCL have generally dismal outcomes, with a median progression-free survival (PFS) of 3.7 months and a median overall survival (OS) of just 6.5 months, according to one study (J Clin Oncol. 2013 Jun 1;31[16]:1970-6).

Courtesy Larry Young

She outlined her center’s approach for treating patients with relapsed or refractory PTCL, following a case presentation by Royal Marsden fellow Matthew Cross, MD.

Complex disease, multiple therapies

The patient was a 71-year-old woman who in 2007 had a diagnosis of asymptomatic stage 4A follicular lymphoma managed with observation; in 2010, she was diagnosed with a CD30-positive PTCL not otherwise specified with ongoing low-level bone marrow involvement with follicular lymphoma.

She initially was treated elsewhere with R-CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab) and had a response after four cycles; however, she had progression with new intra-abdominal nodal sites by the sixth cycle and then was started on two cycles of ESHAP (etoposide, methylprednisolone, high-dose cytarabine, and cisplatin), but she had further progression by May 2011 and opted to forgo additional treatment.

By July 2011, however, she became highly symptomatic with new pruritic rashes on her legs, abdominal pain, and distention. She was referred to the Royal Marsden Hospital, where she was eventually diagnosed with angioimmunoblastic T-cell lymphoma (AITL) with an Epstein-Barr virus–negative clonal large B-cell proliferation in her bone marrow.

She was treated with gemcitabine plus methylprednisolone and prophylactic intrathecal methotrexate and had an “excellent clinical and radiological response,” Dr. Cross said.

A subsequent bone marrow biopsy showed marked hypocellularity but no evidence of either T-cell of B-cell lymphomas.

An autologous stem cell transplant was planned, but two attempts at harvesting peripheral blood stem cells – including one with plerixafor (Mozobil) – failed, and a PET scan within 3 months showed signs of early progression.

In April 2012, the patient was started on romidepsin (Istodax) and had a 1-year remission. But in April 2013, a repeat biopsy again showed CD30-positive AITL. Based on the CD30 positivity, the patient was started on brentuximab vedotin (Adcetris) in May 2013. She was observed to have progression in inguinal nodes in January 2014; she was treated with local radiotherapy and continued on brentuximab but had further progression in June 2014. At that time, she had additional gemcitabine-based combination chemotherapy and had stable disease for 10 months.

In March 2015, she received lenalidomide for further progression but could not tolerate the drug. She died in September 2015, 5 years after diagnosis and 4.5 years after frontline therapy failed.

Therapeutic rationale

Dr. Dearden walked through the choices that she, along with Dr. Cross and their colleagues, made in treating the patient. They chose gemcitabine-based regimens for salvage therapy because of the drug’s efficacy across various forms on non-Hodgkin and Hodgkin lymphoma, she said.

However, a randomized, phase 3, noninferiority trial in the United Kingdom comparing GEM-P (gemcitabine, cisplatin, and methylprednisolone) with CHOP for first-line therapy of PTCL was halted at the interim analysis because GEM-P had not meet the primary endpoint, she said. Results of that trial have not been published to date.

“Clearly, if it’s the patients who do well, often it’s because they achieve a good enough remission to be able to proceed to some sort of consolidation therapy with autologous or allogeneic stem cell transplants, and I think auto-graft is probably accepted for the younger, fitter patients with relapsed chemo-sensitive disease,” she said.

Three-year survival rates for autologous hematopoietic stem cell transplantation range from 36% to 58% and are better than those seen with chemotherapy alone, she said.

“The problem of course is that not many patients receive the planned auto-graft, even if that’s the intention, either because of failure to respond to salvage regimen or early disease progression, which happens before the transplant is able to take place,” she said,

A reasonable alternative for patients with relapsed/refractory PTCL is allogeneic transplantation, as shown in a 2008 study.

Among 77 patients – 57 of whom had received myeloablative conditioning, 31 of whom were in complete remission, and 26 of whom had partial response at the time of transplants – the 5-year treatment-related mortality rate was 33%. However, the 5-year event-free and overall survival rates were 53% and 57%, respectively. Patients with AITL had especially good outcomes (J Clin Oncol. 2008 May 10;26[14]:2264-71).

“In an ideal world, if our patient had been a suitable candidate for an allo-transplant, it’s what we would have tried to undertake,” Dr. Dearden said.

Dr. Dearden recommended that all patients with relapsed or refractory PTCL be considered for clinical trials. For fit patients in first relapse, combination platinum-based chemotherapy followed by autologous or allogeneic transplant may be effective.

For patients not eligible for transplant or with chemotherapy-refractory disease, she recommended trying the following monotherapy approaches: pralatrexate for patients with PTCL not otherwise specified, histone deacetylase inhibitors or 5-azacytidine for AITL, brentuximab vedotin for anaplastic large cell lymphoma, and pembrolizumab for natural killer/T-cell lymphomas.

Although two lines of intensive chemotherapy had failed the case patient within 6 months of diagnosis, she still survived for 5 years with sequential monotherapies, Dr. Dearden noted.

“I use to say to her, ‘You just need to stay one drug ahead of your disease.’ And she was well, she had a very good quality of life for a period of time, and if you can deliver a treatment that is effective for a patient, it will extend their survival,” Dr. Dearden said.

The T-cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization. Dr. Dearden has consulted for MedImmune, Infinity Pharmaceuticals, Janssen, Gilead Sciences, and Roche, and has received honoraria from Janssen and Gilead. Dr. Cross reported no having no financial disclosures.

LA JOLLA, CALIF. – When patients with peripheral T-cell lymphoma (PTCL) experience relapse, consider an allogeneic stem cell transplant or clinical trial, investigators advised.

Patients with relapsed PTCL have generally dismal outcomes, with a median progression-free survival (PFS) of 3.7 months and a median overall survival (OS) of just 6.5 months, according to one study (J Clin Oncol. 2013 Jun 1;31[16]:1970-6).

Courtesy Larry Young

She outlined her center’s approach for treating patients with relapsed or refractory PTCL, following a case presentation by Royal Marsden fellow Matthew Cross, MD.

Complex disease, multiple therapies

The patient was a 71-year-old woman who in 2007 had a diagnosis of asymptomatic stage 4A follicular lymphoma managed with observation; in 2010, she was diagnosed with a CD30-positive PTCL not otherwise specified with ongoing low-level bone marrow involvement with follicular lymphoma.

She initially was treated elsewhere with R-CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab) and had a response after four cycles; however, she had progression with new intra-abdominal nodal sites by the sixth cycle and then was started on two cycles of ESHAP (etoposide, methylprednisolone, high-dose cytarabine, and cisplatin), but she had further progression by May 2011 and opted to forgo additional treatment.

By July 2011, however, she became highly symptomatic with new pruritic rashes on her legs, abdominal pain, and distention. She was referred to the Royal Marsden Hospital, where she was eventually diagnosed with angioimmunoblastic T-cell lymphoma (AITL) with an Epstein-Barr virus–negative clonal large B-cell proliferation in her bone marrow.

She was treated with gemcitabine plus methylprednisolone and prophylactic intrathecal methotrexate and had an “excellent clinical and radiological response,” Dr. Cross said.

A subsequent bone marrow biopsy showed marked hypocellularity but no evidence of either T-cell of B-cell lymphomas.

An autologous stem cell transplant was planned, but two attempts at harvesting peripheral blood stem cells – including one with plerixafor (Mozobil) – failed, and a PET scan within 3 months showed signs of early progression.

In April 2012, the patient was started on romidepsin (Istodax) and had a 1-year remission. But in April 2013, a repeat biopsy again showed CD30-positive AITL. Based on the CD30 positivity, the patient was started on brentuximab vedotin (Adcetris) in May 2013. She was observed to have progression in inguinal nodes in January 2014; she was treated with local radiotherapy and continued on brentuximab but had further progression in June 2014. At that time, she had additional gemcitabine-based combination chemotherapy and had stable disease for 10 months.

In March 2015, she received lenalidomide for further progression but could not tolerate the drug. She died in September 2015, 5 years after diagnosis and 4.5 years after frontline therapy failed.

Therapeutic rationale

Dr. Dearden walked through the choices that she, along with Dr. Cross and their colleagues, made in treating the patient. They chose gemcitabine-based regimens for salvage therapy because of the drug’s efficacy across various forms on non-Hodgkin and Hodgkin lymphoma, she said.

However, a randomized, phase 3, noninferiority trial in the United Kingdom comparing GEM-P (gemcitabine, cisplatin, and methylprednisolone) with CHOP for first-line therapy of PTCL was halted at the interim analysis because GEM-P had not meet the primary endpoint, she said. Results of that trial have not been published to date.

“Clearly, if it’s the patients who do well, often it’s because they achieve a good enough remission to be able to proceed to some sort of consolidation therapy with autologous or allogeneic stem cell transplants, and I think auto-graft is probably accepted for the younger, fitter patients with relapsed chemo-sensitive disease,” she said.

Three-year survival rates for autologous hematopoietic stem cell transplantation range from 36% to 58% and are better than those seen with chemotherapy alone, she said.

“The problem of course is that not many patients receive the planned auto-graft, even if that’s the intention, either because of failure to respond to salvage regimen or early disease progression, which happens before the transplant is able to take place,” she said,

A reasonable alternative for patients with relapsed/refractory PTCL is allogeneic transplantation, as shown in a 2008 study.

Among 77 patients – 57 of whom had received myeloablative conditioning, 31 of whom were in complete remission, and 26 of whom had partial response at the time of transplants – the 5-year treatment-related mortality rate was 33%. However, the 5-year event-free and overall survival rates were 53% and 57%, respectively. Patients with AITL had especially good outcomes (J Clin Oncol. 2008 May 10;26[14]:2264-71).

“In an ideal world, if our patient had been a suitable candidate for an allo-transplant, it’s what we would have tried to undertake,” Dr. Dearden said.

Dr. Dearden recommended that all patients with relapsed or refractory PTCL be considered for clinical trials. For fit patients in first relapse, combination platinum-based chemotherapy followed by autologous or allogeneic transplant may be effective.

For patients not eligible for transplant or with chemotherapy-refractory disease, she recommended trying the following monotherapy approaches: pralatrexate for patients with PTCL not otherwise specified, histone deacetylase inhibitors or 5-azacytidine for AITL, brentuximab vedotin for anaplastic large cell lymphoma, and pembrolizumab for natural killer/T-cell lymphomas.

Although two lines of intensive chemotherapy had failed the case patient within 6 months of diagnosis, she still survived for 5 years with sequential monotherapies, Dr. Dearden noted.

“I use to say to her, ‘You just need to stay one drug ahead of your disease.’ And she was well, she had a very good quality of life for a period of time, and if you can deliver a treatment that is effective for a patient, it will extend their survival,” Dr. Dearden said.

The T-cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization. Dr. Dearden has consulted for MedImmune, Infinity Pharmaceuticals, Janssen, Gilead Sciences, and Roche, and has received honoraria from Janssen and Gilead. Dr. Cross reported no having no financial disclosures.

LA JOLLA, CALIF. – Patients with mycosis fungoides are at increased risk for developing other cancers and should be screened for second primary and hematologic malignancies, results of a cancer registry survey suggest.

A study of data on 6,196 patients included in 18 population-based cancer registries comprising the SEER-18 (Surveillance, Epidemiology, and End Results 18) database who were diagnosed and followed from 2000 to 2014 showed that 514 (8.3%) developed second cancers, compared with the 70.8 secondary malignancies that would be expected in the general population. This difference translated into a standardized incidence ratio (SIR) of 7.3, reported Amrita Goyal, MD, and Aleksandr Lazaryan, MD, PhD, of the University of Minnesota, Minneapolis.

Neil Osterweil/Frontline Medical News

hematologynews@frontlinemedcom.com

SOURCE: Goyal A et al. TCLF 2018 Abstract EP18_2.

LA JOLLA, CALIF. – Patients with mycosis fungoides are at increased risk for developing other cancers and should be screened for second primary and hematologic malignancies, results of a cancer registry survey suggest.

A study of data on 6,196 patients included in 18 population-based cancer registries comprising the SEER-18 (Surveillance, Epidemiology, and End Results 18) database who were diagnosed and followed from 2000 to 2014 showed that 514 (8.3%) developed second cancers, compared with the 70.8 secondary malignancies that would be expected in the general population. This difference translated into a standardized incidence ratio (SIR) of 7.3, reported Amrita Goyal, MD, and Aleksandr Lazaryan, MD, PhD, of the University of Minnesota, Minneapolis.

Neil Osterweil/Frontline Medical News

hematologynews@frontlinemedcom.com

SOURCE: Goyal A et al. TCLF 2018 Abstract EP18_2.

LA JOLLA, CALIF. – Patients with mycosis fungoides are at increased risk for developing other cancers and should be screened for second primary and hematologic malignancies, results of a cancer registry survey suggest.

A study of data on 6,196 patients included in 18 population-based cancer registries comprising the SEER-18 (Surveillance, Epidemiology, and End Results 18) database who were diagnosed and followed from 2000 to 2014 showed that 514 (8.3%) developed second cancers, compared with the 70.8 secondary malignancies that would be expected in the general population. This difference translated into a standardized incidence ratio (SIR) of 7.3, reported Amrita Goyal, MD, and Aleksandr Lazaryan, MD, PhD, of the University of Minnesota, Minneapolis.

Neil Osterweil/Frontline Medical News

hematologynews@frontlinemedcom.com

SOURCE: Goyal A et al. TCLF 2018 Abstract EP18_2.

LA JOLLA, CALIF. – Combining a radio-labeled, anti-CD25, monoclonal antibody with BEAM chemotherapy appears to be an effective and safe conditioning regimen prior to autologous stem cell transplant in patients with peripheral T-cell lymphoma (PTCL), investigators report.

In a phase 1 trial, median progression-free survival (PFS) was 10.6 months for patients treated with the yttrium-90–labeled, chimeric, anti-CD25 antibody basiliximab (Simulect) at one of three dose levels plus standard dose BEAM (carmustine, etoposide, cytarabine, and melphalan), said Jasmine Zain, MD, of the City of Hope Medical Center in Duarte, Calif.

There have been no significant cases of delayed transplant engraftment or unexpected increases in either mucositis or infectious complications, she said at the annual T-cell Lymphoma Forum.

Courtesy Larry Young

hematologynews@frontlinemedcom.com

SOURCE: Zain J et al. TCLF 2018.

LA JOLLA, CALIF. – Combining a radio-labeled, anti-CD25, monoclonal antibody with BEAM chemotherapy appears to be an effective and safe conditioning regimen prior to autologous stem cell transplant in patients with peripheral T-cell lymphoma (PTCL), investigators report.

In a phase 1 trial, median progression-free survival (PFS) was 10.6 months for patients treated with the yttrium-90–labeled, chimeric, anti-CD25 antibody basiliximab (Simulect) at one of three dose levels plus standard dose BEAM (carmustine, etoposide, cytarabine, and melphalan), said Jasmine Zain, MD, of the City of Hope Medical Center in Duarte, Calif.

There have been no significant cases of delayed transplant engraftment or unexpected increases in either mucositis or infectious complications, she said at the annual T-cell Lymphoma Forum.

Courtesy Larry Young

hematologynews@frontlinemedcom.com

SOURCE: Zain J et al. TCLF 2018.

LA JOLLA, CALIF. – Combining a radio-labeled, anti-CD25, monoclonal antibody with BEAM chemotherapy appears to be an effective and safe conditioning regimen prior to autologous stem cell transplant in patients with peripheral T-cell lymphoma (PTCL), investigators report.

In a phase 1 trial, median progression-free survival (PFS) was 10.6 months for patients treated with the yttrium-90–labeled, chimeric, anti-CD25 antibody basiliximab (Simulect) at one of three dose levels plus standard dose BEAM (carmustine, etoposide, cytarabine, and melphalan), said Jasmine Zain, MD, of the City of Hope Medical Center in Duarte, Calif.

There have been no significant cases of delayed transplant engraftment or unexpected increases in either mucositis or infectious complications, she said at the annual T-cell Lymphoma Forum.

Courtesy Larry Young

hematologynews@frontlinemedcom.com

SOURCE: Zain J et al. TCLF 2018.

Photo by Larry Young

LA JOLLA, CA—An antibody targeting KIR3DL2 has “very promising activity” in relapsed/refractory cutaneous T-cell lymphoma (CTCL), according to a speaker at the 10th Annual T-cell Lymphoma Forum.

The antibody, IPH4102, produced an overall response rate (ORR) of 44% in a phase 1 trial of CTCL patients, with an ORR of 50% in patients with Sézary syndrome (SS).

There were 2 serious adverse events (AEs) that were considered possibly related to IPH4102, and 1 of these was fatal.

Youn H. Kim, MD, of Stanford Cancer Institute in Palo Alto, California, presented these results at this year’s T-cell Lymphoma Forum. The research was sponsored by Innate Pharma, the company developing IPH4102.

“KIR3DL2 is a target that’s a member of the killer immunoglobulin-like receptor [KIR] family, and it’s also very specifically expressed in CTCL,” Dr Kim explained. “The antibody [IPH4102] is Fc-modified to enhance the antibody-dependent cell cytotoxicity and also works by antibody-dependent cell phagocytosis. It binds and, with the immunologic effect, kills the cancer cells.”

“[IPH4102] is specific for cancer cells because [KIR3DL2] is only minimally expressed in normal T cells as well as natural killer [NK] cells. About a third of NK cells that do express [KIR3DL2] don’t get affected [by IPH4102]. So it looks like the killer cells don’t kill each other, and they specifically target the neoplastic cells.”

Patients

Dr Kim and her colleagues have tested IPH4102 in 25 patients with relapsed/refractory CTCL—20 with SS, 4 with mycosis fungoides (MF), and 1 with CD4+ CTCL not otherwise specified. At baseline, patients had a median age of 71 (range, 42-90).

The patients had received a median of 4 prior systemic regimens (range, 2-10). Among the MF and SS patients, 1 patient had stage IB disease, 3 had stage IIB, and 20 had stage IVA disease.

Treatment

This study has a dose-escalation portion (accelerated 3+3 design) and an expansion portion. Dr Kim presented results for the 25 patients in the dose-escalation portion, which was completed in May 2017.

Patients received IPH4102 at 10 dose levels, ranging from 0.0001 mg/kg to 10 mg/kg. They received the drug once weekly for 4 doses, every 2 weeks for 10 doses, and every 4 weeks thereafter. They were treated until progression or unacceptable toxicity.

The expansion cohorts (which include SS and transformed MF patients) started enrolling in July 2017, with patients receiving IPH4102 at the recommended phase 2 dose—750 mg.

Safety

There were no dose-limiting toxicities with IPH4102. So the equivalent of 10 mg/kg—a 750 mg flat dose—was deemed the recommended phase 2 (and expansion) dose.

The incidence of AEs was 92% (n=23), and the incidence of treatment-related AEs was 52% (n=13).

Treatment-related AEs included lymphopenia (16%, n=4), asthenia (12%, n=3), nausea (8%, n=2), chills (8%, n=2), pyrexia (8%, n=2), arthralgia (8%, n=2), and muscle spasms (8%, n=2).

Eight patients had serious AEs, and 2 had serious AEs that were considered possibly related to treatment.

One patient had grade 2 atrial flutter diagnosed 1 hour after the first dose of IPH4102. The patient had a history of cardiac arrhythmia. She was hospitalized after the atrial flutter, received amiodarone, and the arrhythmia resolved. She went on to receive 15 more doses of IPH4102 without recurrence.

The other patient with a serious AE considered possibly related to treatment had hepatitis that occurred 6 weeks after the last dose of IPH4102. The patient had discontinued treatment due to progression after receiving IPH4102 for a year and achieving a partial response (PR).

This patient ultimately died of the hepatitis. Another fatal AE, considered unrelated to treatment, was Staphylococcus aureus sepsis.

“The safety looks very solid,” Dr Kim said, “[with] very low numbers of any significant severe adverse effects.”

Efficacy

The best global ORR was 44%, with 10 PRs and 1 complete response (CR). Twelve patients had stable disease, and 2 progressed.

In patients with SS, the best global ORR was 50%. One patient had a CR, 9 had PRs, and 8 had stable disease. The ORR was 60% in the skin and a 65% in the blood compartment for patients with SS.

Four responses were ongoing at last follow-up. The median follow-up was 15 months.

The median duration of response for the entire cohort was 8.2 months (range, 64 days to 519+ days). For SS patients, the median duration of response was 9.9 months (range, 64 days to 519+ days).

The median progression-free survival was 9.8 months overall (range, 28 days to 610+ days). For SS patients, the median progression-free survival was 10.8 months (range, 28 days to 610+ days).

“So with the efficacy and the safety profile, we are really hoping to get this drug to the phase 2 level and are excited to move forward,” Dr Kim concluded.

Photo by Larry Young

LA JOLLA, CA—An antibody targeting KIR3DL2 has “very promising activity” in relapsed/refractory cutaneous T-cell lymphoma (CTCL), according to a speaker at the 10th Annual T-cell Lymphoma Forum.

The antibody, IPH4102, produced an overall response rate (ORR) of 44% in a phase 1 trial of CTCL patients, with an ORR of 50% in patients with Sézary syndrome (SS).

There were 2 serious adverse events (AEs) that were considered possibly related to IPH4102, and 1 of these was fatal.

Youn H. Kim, MD, of Stanford Cancer Institute in Palo Alto, California, presented these results at this year’s T-cell Lymphoma Forum. The research was sponsored by Innate Pharma, the company developing IPH4102.

“KIR3DL2 is a target that’s a member of the killer immunoglobulin-like receptor [KIR] family, and it’s also very specifically expressed in CTCL,” Dr Kim explained. “The antibody [IPH4102] is Fc-modified to enhance the antibody-dependent cell cytotoxicity and also works by antibody-dependent cell phagocytosis. It binds and, with the immunologic effect, kills the cancer cells.”

“[IPH4102] is specific for cancer cells because [KIR3DL2] is only minimally expressed in normal T cells as well as natural killer [NK] cells. About a third of NK cells that do express [KIR3DL2] don’t get affected [by IPH4102]. So it looks like the killer cells don’t kill each other, and they specifically target the neoplastic cells.”

Patients

Dr Kim and her colleagues have tested IPH4102 in 25 patients with relapsed/refractory CTCL—20 with SS, 4 with mycosis fungoides (MF), and 1 with CD4+ CTCL not otherwise specified. At baseline, patients had a median age of 71 (range, 42-90).

The patients had received a median of 4 prior systemic regimens (range, 2-10). Among the MF and SS patients, 1 patient had stage IB disease, 3 had stage IIB, and 20 had stage IVA disease.

Treatment

This study has a dose-escalation portion (accelerated 3+3 design) and an expansion portion. Dr Kim presented results for the 25 patients in the dose-escalation portion, which was completed in May 2017.

Patients received IPH4102 at 10 dose levels, ranging from 0.0001 mg/kg to 10 mg/kg. They received the drug once weekly for 4 doses, every 2 weeks for 10 doses, and every 4 weeks thereafter. They were treated until progression or unacceptable toxicity.

The expansion cohorts (which include SS and transformed MF patients) started enrolling in July 2017, with patients receiving IPH4102 at the recommended phase 2 dose—750 mg.

Safety

There were no dose-limiting toxicities with IPH4102. So the equivalent of 10 mg/kg—a 750 mg flat dose—was deemed the recommended phase 2 (and expansion) dose.

The incidence of AEs was 92% (n=23), and the incidence of treatment-related AEs was 52% (n=13).

Treatment-related AEs included lymphopenia (16%, n=4), asthenia (12%, n=3), nausea (8%, n=2), chills (8%, n=2), pyrexia (8%, n=2), arthralgia (8%, n=2), and muscle spasms (8%, n=2).

Eight patients had serious AEs, and 2 had serious AEs that were considered possibly related to treatment.

One patient had grade 2 atrial flutter diagnosed 1 hour after the first dose of IPH4102. The patient had a history of cardiac arrhythmia. She was hospitalized after the atrial flutter, received amiodarone, and the arrhythmia resolved. She went on to receive 15 more doses of IPH4102 without recurrence.

The other patient with a serious AE considered possibly related to treatment had hepatitis that occurred 6 weeks after the last dose of IPH4102. The patient had discontinued treatment due to progression after receiving IPH4102 for a year and achieving a partial response (PR).

This patient ultimately died of the hepatitis. Another fatal AE, considered unrelated to treatment, was Staphylococcus aureus sepsis.

“The safety looks very solid,” Dr Kim said, “[with] very low numbers of any significant severe adverse effects.”

Efficacy

The best global ORR was 44%, with 10 PRs and 1 complete response (CR). Twelve patients had stable disease, and 2 progressed.

In patients with SS, the best global ORR was 50%. One patient had a CR, 9 had PRs, and 8 had stable disease. The ORR was 60% in the skin and a 65% in the blood compartment for patients with SS.

Four responses were ongoing at last follow-up. The median follow-up was 15 months.

The median duration of response for the entire cohort was 8.2 months (range, 64 days to 519+ days). For SS patients, the median duration of response was 9.9 months (range, 64 days to 519+ days).

The median progression-free survival was 9.8 months overall (range, 28 days to 610+ days). For SS patients, the median progression-free survival was 10.8 months (range, 28 days to 610+ days).

“So with the efficacy and the safety profile, we are really hoping to get this drug to the phase 2 level and are excited to move forward,” Dr Kim concluded.

Photo by Larry Young

LA JOLLA, CA—An antibody targeting KIR3DL2 has “very promising activity” in relapsed/refractory cutaneous T-cell lymphoma (CTCL), according to a speaker at the 10th Annual T-cell Lymphoma Forum.

The antibody, IPH4102, produced an overall response rate (ORR) of 44% in a phase 1 trial of CTCL patients, with an ORR of 50% in patients with Sézary syndrome (SS).

There were 2 serious adverse events (AEs) that were considered possibly related to IPH4102, and 1 of these was fatal.

Youn H. Kim, MD, of Stanford Cancer Institute in Palo Alto, California, presented these results at this year’s T-cell Lymphoma Forum. The research was sponsored by Innate Pharma, the company developing IPH4102.

“KIR3DL2 is a target that’s a member of the killer immunoglobulin-like receptor [KIR] family, and it’s also very specifically expressed in CTCL,” Dr Kim explained. “The antibody [IPH4102] is Fc-modified to enhance the antibody-dependent cell cytotoxicity and also works by antibody-dependent cell phagocytosis. It binds and, with the immunologic effect, kills the cancer cells.”

“[IPH4102] is specific for cancer cells because [KIR3DL2] is only minimally expressed in normal T cells as well as natural killer [NK] cells. About a third of NK cells that do express [KIR3DL2] don’t get affected [by IPH4102]. So it looks like the killer cells don’t kill each other, and they specifically target the neoplastic cells.”

Patients

Dr Kim and her colleagues have tested IPH4102 in 25 patients with relapsed/refractory CTCL—20 with SS, 4 with mycosis fungoides (MF), and 1 with CD4+ CTCL not otherwise specified. At baseline, patients had a median age of 71 (range, 42-90).

The patients had received a median of 4 prior systemic regimens (range, 2-10). Among the MF and SS patients, 1 patient had stage IB disease, 3 had stage IIB, and 20 had stage IVA disease.

Treatment

This study has a dose-escalation portion (accelerated 3+3 design) and an expansion portion. Dr Kim presented results for the 25 patients in the dose-escalation portion, which was completed in May 2017.

Patients received IPH4102 at 10 dose levels, ranging from 0.0001 mg/kg to 10 mg/kg. They received the drug once weekly for 4 doses, every 2 weeks for 10 doses, and every 4 weeks thereafter. They were treated until progression or unacceptable toxicity.

The expansion cohorts (which include SS and transformed MF patients) started enrolling in July 2017, with patients receiving IPH4102 at the recommended phase 2 dose—750 mg.

Safety

There were no dose-limiting toxicities with IPH4102. So the equivalent of 10 mg/kg—a 750 mg flat dose—was deemed the recommended phase 2 (and expansion) dose.

The incidence of AEs was 92% (n=23), and the incidence of treatment-related AEs was 52% (n=13).

Treatment-related AEs included lymphopenia (16%, n=4), asthenia (12%, n=3), nausea (8%, n=2), chills (8%, n=2), pyrexia (8%, n=2), arthralgia (8%, n=2), and muscle spasms (8%, n=2).

Eight patients had serious AEs, and 2 had serious AEs that were considered possibly related to treatment.

One patient had grade 2 atrial flutter diagnosed 1 hour after the first dose of IPH4102. The patient had a history of cardiac arrhythmia. She was hospitalized after the atrial flutter, received amiodarone, and the arrhythmia resolved. She went on to receive 15 more doses of IPH4102 without recurrence.

The other patient with a serious AE considered possibly related to treatment had hepatitis that occurred 6 weeks after the last dose of IPH4102. The patient had discontinued treatment due to progression after receiving IPH4102 for a year and achieving a partial response (PR).

This patient ultimately died of the hepatitis. Another fatal AE, considered unrelated to treatment, was Staphylococcus aureus sepsis.

“The safety looks very solid,” Dr Kim said, “[with] very low numbers of any significant severe adverse effects.”

Efficacy

The best global ORR was 44%, with 10 PRs and 1 complete response (CR). Twelve patients had stable disease, and 2 progressed.

In patients with SS, the best global ORR was 50%. One patient had a CR, 9 had PRs, and 8 had stable disease. The ORR was 60% in the skin and a 65% in the blood compartment for patients with SS.

Four responses were ongoing at last follow-up. The median follow-up was 15 months.

The median duration of response for the entire cohort was 8.2 months (range, 64 days to 519+ days). For SS patients, the median duration of response was 9.9 months (range, 64 days to 519+ days).

The median progression-free survival was 9.8 months overall (range, 28 days to 610+ days). For SS patients, the median progression-free survival was 10.8 months (range, 28 days to 610+ days).

“So with the efficacy and the safety profile, we are really hoping to get this drug to the phase 2 level and are excited to move forward,” Dr Kim concluded.

LA JOLLA, CALIF. – For patients with relapsed peripheral T-cell lymphoma, allogeneic stem cell transplants offer the best chance for achieving remission or even a cure, making the choice of therapies as bridges to transplant essential for getting there.

“The goal is to get to transplant with a curative intent. In our hands, that’s mostly allo[geneic] and mostly in the relapsed setting,” Steven M. Horwitz, MD, from the lymphoma service at Memorial Sloan Kettering Cancer Center, New York, said at the annual T-cell Lymphoma Forum. “The best bridge to transplant is the one that gets you across safely.”

Courtesy Larry Young

Better approaches by subtype?

The subtype of PTCL also appears to matter. Three approved agents for relapsed/refractory PTCL – belinostat (Beleodaq), romidepsin (Istodax), and pralatrexate (Folotyn) – are associated with CR rates of 11%, 15%, and 11%, respectively. But one PTCL subtype, anaplastic large cell lymphoma, appears particularly sensitive to treatment with brentuximab vedotin (Adcetris), with CR rates of 59%, Dr. Horwitz noted.

In a 2014 study, investigators reported that of the nine patients with anaplastic large cell lymphoma positive for anaplastic lymphoma kinase and treated with the anaplastic lymphoma kinase inhibitor crizotinib (Xalkori), all had a CR, with response durations stretching pasting 40 months in one patient, and past 30 months in two others (J Natl Cancer Inst. 2014 Feb;106[2]:djt378).

A different subtype, natural killer/T-cell lymphoma, was shown to be responsive to immunotherapy with pembrolizumab (Keytruda) in seven patients, with CRs in five and partial remissions in two. Responses to pembrolizumab in this PTCL subtype may be adequately long for getting patients to transplant, Dr. Horwitz said.

For some patients with angioimmunoblastic T-cell lymphoma, therapy with epigenetic modifying agents, such as decitabine or a combination of romidepsin and lenalidomide (Revlimid), with or without carfilzomib (Kyprolis), may also be effective bridges to transplant, based on the best available evidence.
 

Timing may also matter

Dr. Horwitz cautioned that for patients with cutaneous T-cell lymphoma, the investigational agent mogamulizumab, which was shown in the MAVORIC (Study of KW-0761 versus Vorinostat in Relapsed/Refractory CTCL) trial to offer significantly better PFS compared with vorinostat (Zolinza), also appears to increase the chance that patients will develop high-risk, potentially fatal graft vs. host disease posttransplant.

The risk appears to be slightly lower among patients who received the last dose of mogamulizumab more than 50 days before undergoing SCT, he noted.

Although there is no strong evidence to support it, Dr. Horwitz noted that the timing of most other therapies may also be important to the success of SCT. “I think we have seen that when patients have a big [long] break before transplant, the relapse rate is high, and I have a personal preference for using regimens that you can continue up close to transplant, because I think we lose [fewer] patients getting ready for that,” he said.

Dr. Horwitz had previously disclosed financial relationships with Celgene, Forty Seven, Huya Bioscience International, Infinity, Kyowa Hakko Kirin, Millennium, Seattle Genetics, and Takeda. The T-Cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization.

hematologynews@frontlinemedcom.com

LA JOLLA, CALIF. – For patients with relapsed peripheral T-cell lymphoma, allogeneic stem cell transplants offer the best chance for achieving remission or even a cure, making the choice of therapies as bridges to transplant essential for getting there.

“The goal is to get to transplant with a curative intent. In our hands, that’s mostly allo[geneic] and mostly in the relapsed setting,” Steven M. Horwitz, MD, from the lymphoma service at Memorial Sloan Kettering Cancer Center, New York, said at the annual T-cell Lymphoma Forum. “The best bridge to transplant is the one that gets you across safely.”

Courtesy Larry Young

Better approaches by subtype?

The subtype of PTCL also appears to matter. Three approved agents for relapsed/refractory PTCL – belinostat (Beleodaq), romidepsin (Istodax), and pralatrexate (Folotyn) – are associated with CR rates of 11%, 15%, and 11%, respectively. But one PTCL subtype, anaplastic large cell lymphoma, appears particularly sensitive to treatment with brentuximab vedotin (Adcetris), with CR rates of 59%, Dr. Horwitz noted.

In a 2014 study, investigators reported that of the nine patients with anaplastic large cell lymphoma positive for anaplastic lymphoma kinase and treated with the anaplastic lymphoma kinase inhibitor crizotinib (Xalkori), all had a CR, with response durations stretching pasting 40 months in one patient, and past 30 months in two others (J Natl Cancer Inst. 2014 Feb;106[2]:djt378).

A different subtype, natural killer/T-cell lymphoma, was shown to be responsive to immunotherapy with pembrolizumab (Keytruda) in seven patients, with CRs in five and partial remissions in two. Responses to pembrolizumab in this PTCL subtype may be adequately long for getting patients to transplant, Dr. Horwitz said.

For some patients with angioimmunoblastic T-cell lymphoma, therapy with epigenetic modifying agents, such as decitabine or a combination of romidepsin and lenalidomide (Revlimid), with or without carfilzomib (Kyprolis), may also be effective bridges to transplant, based on the best available evidence.
 

Timing may also matter

Dr. Horwitz cautioned that for patients with cutaneous T-cell lymphoma, the investigational agent mogamulizumab, which was shown in the MAVORIC (Study of KW-0761 versus Vorinostat in Relapsed/Refractory CTCL) trial to offer significantly better PFS compared with vorinostat (Zolinza), also appears to increase the chance that patients will develop high-risk, potentially fatal graft vs. host disease posttransplant.

The risk appears to be slightly lower among patients who received the last dose of mogamulizumab more than 50 days before undergoing SCT, he noted.

Although there is no strong evidence to support it, Dr. Horwitz noted that the timing of most other therapies may also be important to the success of SCT. “I think we have seen that when patients have a big [long] break before transplant, the relapse rate is high, and I have a personal preference for using regimens that you can continue up close to transplant, because I think we lose [fewer] patients getting ready for that,” he said.

Dr. Horwitz had previously disclosed financial relationships with Celgene, Forty Seven, Huya Bioscience International, Infinity, Kyowa Hakko Kirin, Millennium, Seattle Genetics, and Takeda. The T-Cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization.

hematologynews@frontlinemedcom.com

LA JOLLA, CALIF. – For patients with relapsed peripheral T-cell lymphoma, allogeneic stem cell transplants offer the best chance for achieving remission or even a cure, making the choice of therapies as bridges to transplant essential for getting there.

“The goal is to get to transplant with a curative intent. In our hands, that’s mostly allo[geneic] and mostly in the relapsed setting,” Steven M. Horwitz, MD, from the lymphoma service at Memorial Sloan Kettering Cancer Center, New York, said at the annual T-cell Lymphoma Forum. “The best bridge to transplant is the one that gets you across safely.”

Courtesy Larry Young

Better approaches by subtype?

The subtype of PTCL also appears to matter. Three approved agents for relapsed/refractory PTCL – belinostat (Beleodaq), romidepsin (Istodax), and pralatrexate (Folotyn) – are associated with CR rates of 11%, 15%, and 11%, respectively. But one PTCL subtype, anaplastic large cell lymphoma, appears particularly sensitive to treatment with brentuximab vedotin (Adcetris), with CR rates of 59%, Dr. Horwitz noted.

In a 2014 study, investigators reported that of the nine patients with anaplastic large cell lymphoma positive for anaplastic lymphoma kinase and treated with the anaplastic lymphoma kinase inhibitor crizotinib (Xalkori), all had a CR, with response durations stretching pasting 40 months in one patient, and past 30 months in two others (J Natl Cancer Inst. 2014 Feb;106[2]:djt378).

A different subtype, natural killer/T-cell lymphoma, was shown to be responsive to immunotherapy with pembrolizumab (Keytruda) in seven patients, with CRs in five and partial remissions in two. Responses to pembrolizumab in this PTCL subtype may be adequately long for getting patients to transplant, Dr. Horwitz said.

For some patients with angioimmunoblastic T-cell lymphoma, therapy with epigenetic modifying agents, such as decitabine or a combination of romidepsin and lenalidomide (Revlimid), with or without carfilzomib (Kyprolis), may also be effective bridges to transplant, based on the best available evidence.
 

Timing may also matter

Dr. Horwitz cautioned that for patients with cutaneous T-cell lymphoma, the investigational agent mogamulizumab, which was shown in the MAVORIC (Study of KW-0761 versus Vorinostat in Relapsed/Refractory CTCL) trial to offer significantly better PFS compared with vorinostat (Zolinza), also appears to increase the chance that patients will develop high-risk, potentially fatal graft vs. host disease posttransplant.

The risk appears to be slightly lower among patients who received the last dose of mogamulizumab more than 50 days before undergoing SCT, he noted.

Although there is no strong evidence to support it, Dr. Horwitz noted that the timing of most other therapies may also be important to the success of SCT. “I think we have seen that when patients have a big [long] break before transplant, the relapse rate is high, and I have a personal preference for using regimens that you can continue up close to transplant, because I think we lose [fewer] patients getting ready for that,” he said.

Dr. Horwitz had previously disclosed financial relationships with Celgene, Forty Seven, Huya Bioscience International, Infinity, Kyowa Hakko Kirin, Millennium, Seattle Genetics, and Takeda. The T-Cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization.

hematologynews@frontlinemedcom.com

Photo by Larry Young

LA JOLLA, CA—The dual PI3K δ/γ inhibitor tenalisib has demonstrated activity in a phase 1 trial of patients with relapsed/refractory T-cell lymphomas.

Tenalisib produced “encouraging” response rates of 44% in patients with cutaneous T-cell lymphoma (CTCL) and 50% in patients with peripheral T-cell lymphoma (PTCL), according to study investigator Bradley M. Haverkos, MD, of the University of Colorado School of Medicine in Aurora.

Dr Haverkos also said tenalisib had an acceptable safety profile.

The most common treatment-related adverse event (AE) in both patient groups was transaminitis.

Dr Haverkos and his colleagues presented these results in a pair of posters and an oral presentation at the 10th Annual T-cell Lymphoma Forum.

The trial was sponsored by Rhizen Pharmaceuticals, the company developing tenalisib (formerly RP6530).

The researchers have enrolled 55 patients in this trial—28 with CTCL and 27 with PTCL.

The study has a standard 3+3 design, starting with a 200 mg daily fasting dose of tenalisib and escalating to an 800 mg daily fasting dose, followed by an 800 mg daily fed cohort.

There were 3 dose-limiting toxicities in the 800 mg fed cohort—transaminitis, rash, and neutropenia. Therefore, the 800 mg fasting dose was considered the maximum-tolerated dose.

Patients in the PTCL and CTCL expansion cohorts received the maximum-tolerated dose.

Patients were scheduled to receive 8 cycles (28 days each) of tenalisib, but treatment could be extended to 24 months.

The data cutoff was January 10, 2018.

Efficacy in PTCL

Most PTCL patients (n=24) had PTCL not otherwise specified (NOS), 2 had angioimmunoblastic T-cell lymphoma (AITL), and 1 had subcutaneous panniculitis-like T-cell lymphoma (SPTCL).

The patients’ median age at baseline was 63 (range, 40-89), and 63% are male. Sixty-three percent of patients had relapsed disease at baseline, 37% were refractory, and 93% had stage 3 or 4 disease. Patients had received a median of 3 prior therapies (range, 1-7).

The median duration of treatment with tenalisib was 1.9 months.

Fourteen patients were evaluable for efficacy. Eleven patients had progressed prior to the first protocol-defined assessment, and 2 patients had not reached their first efficacy assessment at the data cutoff.

Seven of the 14 evaluable patients responded (50%). Three patients (21%) had a complete response (CR), 4 (29%) had a partial response (PR), 3 (21%) had stable disease, and 4 (29%) progressed.

“There were several patients with lengthy responses,” Dr Haverkos noted. “One patient had an ongoing response at 16 months, another at 11 months, and a number of patients had ongoing responses at 7 months.”

All 3 patients with a CR had PTCL NOS and received the 800 mg fasting dose of tenalisib.

Two patients with a PR had PTCL NOS, 1 had AITL, and 1 had SPTCL. The SPTCL patient received the 200 mg dose.

The AITL patient and 1 of the PTCL NOS patients received the 800 mg fasting dose. The other PTCL NOS patient received the 400 mg dose.

Efficacy in CTCL

Most CTCL patients (n=23) had mycosis fungoides, but 5 had Sézary syndrome. The patients’ median age at baseline was 68 (range, 39-84), and 57% are female.

Forty-three percent of patients had relapsed disease at baseline, 57% were refractory, and 46% had stage 3 or 4 disease. Patients had received a median of 6 prior therapies (range, 2-15).

The median duration of treatment with tenalisib was 3.4 months.

Eighteen patients were evaluable for efficacy. Eight patients had progressed prior to the first protocol-defined assessment, and 2 patients had not yet reached their first efficacy assessment.

Eight of the 18 evaluable patients responded (44%), all with PRs. Seven patients (39%) had stable disease, and 3 (17%) progressed.

Four patients were still in response beyond 8 months of follow-up, and 1 patient was still in PR beyond 11 months.

Five patients with a PR had received the 800 mg fasting dose of tenalisib. Two received the 800 mg fed dose, and 1 patient received the drug at 400 mg.

Overall safety

Treatment-related AEs included transaminitis (25%, 14/55), diarrhea (11%, n=6), fatigue (6%, n=11), headache (9%, n=5), rash (9%, n=5), nausea (5%, n=3), vomiting (5%, n=3), pyrexia (5%, n=3), and dizziness (5%, n=3). Dizziness was only observed in CTCL patients.

Treatment-related grade 3 or higher AEs included transaminitis (20%, n=11), rash (5%, n=3), neutropenia (2%, n=1), hypophosphatemia (2%, n=1), international normalized ratio increase (2%, n=1), sepsis (2%, n=1), pyrexia (2%, n=1), and diplopia secondary to neuropathy (2%, n=1).

Seventy-six percent (n=42) of patients discontinued treatment. Sixty-eight percent (n=29) stopped due to progression, 5% (n=2) stopped at investigators’ discretion, 9% (n=4) withdrew consent, 12% (n=5) had a treatment-related AE, and 5% (n=2) had an unrelated AE.

Seventeen PTCL patients stopped treatment due to progression, as did 12 CTCL patients. One patient in each group stopped treatment at investigators’ discretion, and all 4 patients who withdrew consent had CTCL.

Four CTCL patients stopped treatment due to a related AE—transaminitis, sepsis, diarrhea, and diplopia secondary to neuropathy. One PTCL patient stopped treatment due to a related AE, which was transaminitis.

“Tenalisib at the 800 mg fasting dose has demonstrated acceptable safety and tolerability,” Dr Haverkos concluded. “We’ve observed encouraging response rates thus far, which support further evaluation of tenalisib in these patients.”

Photo by Larry Young

LA JOLLA, CA—The dual PI3K δ/γ inhibitor tenalisib has demonstrated activity in a phase 1 trial of patients with relapsed/refractory T-cell lymphomas.

Tenalisib produced “encouraging” response rates of 44% in patients with cutaneous T-cell lymphoma (CTCL) and 50% in patients with peripheral T-cell lymphoma (PTCL), according to study investigator Bradley M. Haverkos, MD, of the University of Colorado School of Medicine in Aurora.

Dr Haverkos also said tenalisib had an acceptable safety profile.

The most common treatment-related adverse event (AE) in both patient groups was transaminitis.

Dr Haverkos and his colleagues presented these results in a pair of posters and an oral presentation at the 10th Annual T-cell Lymphoma Forum.

The trial was sponsored by Rhizen Pharmaceuticals, the company developing tenalisib (formerly RP6530).

The researchers have enrolled 55 patients in this trial—28 with CTCL and 27 with PTCL.

The study has a standard 3+3 design, starting with a 200 mg daily fasting dose of tenalisib and escalating to an 800 mg daily fasting dose, followed by an 800 mg daily fed cohort.

There were 3 dose-limiting toxicities in the 800 mg fed cohort—transaminitis, rash, and neutropenia. Therefore, the 800 mg fasting dose was considered the maximum-tolerated dose.

Patients in the PTCL and CTCL expansion cohorts received the maximum-tolerated dose.

Patients were scheduled to receive 8 cycles (28 days each) of tenalisib, but treatment could be extended to 24 months.

The data cutoff was January 10, 2018.

Efficacy in PTCL

Most PTCL patients (n=24) had PTCL not otherwise specified (NOS), 2 had angioimmunoblastic T-cell lymphoma (AITL), and 1 had subcutaneous panniculitis-like T-cell lymphoma (SPTCL).

The patients’ median age at baseline was 63 (range, 40-89), and 63% are male. Sixty-three percent of patients had relapsed disease at baseline, 37% were refractory, and 93% had stage 3 or 4 disease. Patients had received a median of 3 prior therapies (range, 1-7).

The median duration of treatment with tenalisib was 1.9 months.

Fourteen patients were evaluable for efficacy. Eleven patients had progressed prior to the first protocol-defined assessment, and 2 patients had not reached their first efficacy assessment at the data cutoff.

Seven of the 14 evaluable patients responded (50%). Three patients (21%) had a complete response (CR), 4 (29%) had a partial response (PR), 3 (21%) had stable disease, and 4 (29%) progressed.

“There were several patients with lengthy responses,” Dr Haverkos noted. “One patient had an ongoing response at 16 months, another at 11 months, and a number of patients had ongoing responses at 7 months.”

All 3 patients with a CR had PTCL NOS and received the 800 mg fasting dose of tenalisib.

Two patients with a PR had PTCL NOS, 1 had AITL, and 1 had SPTCL. The SPTCL patient received the 200 mg dose.

The AITL patient and 1 of the PTCL NOS patients received the 800 mg fasting dose. The other PTCL NOS patient received the 400 mg dose.

Efficacy in CTCL

Most CTCL patients (n=23) had mycosis fungoides, but 5 had Sézary syndrome. The patients’ median age at baseline was 68 (range, 39-84), and 57% are female.

Forty-three percent of patients had relapsed disease at baseline, 57% were refractory, and 46% had stage 3 or 4 disease. Patients had received a median of 6 prior therapies (range, 2-15).

The median duration of treatment with tenalisib was 3.4 months.

Eighteen patients were evaluable for efficacy. Eight patients had progressed prior to the first protocol-defined assessment, and 2 patients had not yet reached their first efficacy assessment.

Eight of the 18 evaluable patients responded (44%), all with PRs. Seven patients (39%) had stable disease, and 3 (17%) progressed.

Four patients were still in response beyond 8 months of follow-up, and 1 patient was still in PR beyond 11 months.

Five patients with a PR had received the 800 mg fasting dose of tenalisib. Two received the 800 mg fed dose, and 1 patient received the drug at 400 mg.

Overall safety

Treatment-related AEs included transaminitis (25%, 14/55), diarrhea (11%, n=6), fatigue (6%, n=11), headache (9%, n=5), rash (9%, n=5), nausea (5%, n=3), vomiting (5%, n=3), pyrexia (5%, n=3), and dizziness (5%, n=3). Dizziness was only observed in CTCL patients.

Treatment-related grade 3 or higher AEs included transaminitis (20%, n=11), rash (5%, n=3), neutropenia (2%, n=1), hypophosphatemia (2%, n=1), international normalized ratio increase (2%, n=1), sepsis (2%, n=1), pyrexia (2%, n=1), and diplopia secondary to neuropathy (2%, n=1).

Seventy-six percent (n=42) of patients discontinued treatment. Sixty-eight percent (n=29) stopped due to progression, 5% (n=2) stopped at investigators’ discretion, 9% (n=4) withdrew consent, 12% (n=5) had a treatment-related AE, and 5% (n=2) had an unrelated AE.

Seventeen PTCL patients stopped treatment due to progression, as did 12 CTCL patients. One patient in each group stopped treatment at investigators’ discretion, and all 4 patients who withdrew consent had CTCL.

Four CTCL patients stopped treatment due to a related AE—transaminitis, sepsis, diarrhea, and diplopia secondary to neuropathy. One PTCL patient stopped treatment due to a related AE, which was transaminitis.

“Tenalisib at the 800 mg fasting dose has demonstrated acceptable safety and tolerability,” Dr Haverkos concluded. “We’ve observed encouraging response rates thus far, which support further evaluation of tenalisib in these patients.”

Photo by Larry Young

LA JOLLA, CA—The dual PI3K δ/γ inhibitor tenalisib has demonstrated activity in a phase 1 trial of patients with relapsed/refractory T-cell lymphomas.

Tenalisib produced “encouraging” response rates of 44% in patients with cutaneous T-cell lymphoma (CTCL) and 50% in patients with peripheral T-cell lymphoma (PTCL), according to study investigator Bradley M. Haverkos, MD, of the University of Colorado School of Medicine in Aurora.

Dr Haverkos also said tenalisib had an acceptable safety profile.

The most common treatment-related adverse event (AE) in both patient groups was transaminitis.

Dr Haverkos and his colleagues presented these results in a pair of posters and an oral presentation at the 10th Annual T-cell Lymphoma Forum.

The trial was sponsored by Rhizen Pharmaceuticals, the company developing tenalisib (formerly RP6530).

The researchers have enrolled 55 patients in this trial—28 with CTCL and 27 with PTCL.

The study has a standard 3+3 design, starting with a 200 mg daily fasting dose of tenalisib and escalating to an 800 mg daily fasting dose, followed by an 800 mg daily fed cohort.

There were 3 dose-limiting toxicities in the 800 mg fed cohort—transaminitis, rash, and neutropenia. Therefore, the 800 mg fasting dose was considered the maximum-tolerated dose.

Patients in the PTCL and CTCL expansion cohorts received the maximum-tolerated dose.

Patients were scheduled to receive 8 cycles (28 days each) of tenalisib, but treatment could be extended to 24 months.

The data cutoff was January 10, 2018.

Efficacy in PTCL

Most PTCL patients (n=24) had PTCL not otherwise specified (NOS), 2 had angioimmunoblastic T-cell lymphoma (AITL), and 1 had subcutaneous panniculitis-like T-cell lymphoma (SPTCL).

The patients’ median age at baseline was 63 (range, 40-89), and 63% are male. Sixty-three percent of patients had relapsed disease at baseline, 37% were refractory, and 93% had stage 3 or 4 disease. Patients had received a median of 3 prior therapies (range, 1-7).

The median duration of treatment with tenalisib was 1.9 months.

Fourteen patients were evaluable for efficacy. Eleven patients had progressed prior to the first protocol-defined assessment, and 2 patients had not reached their first efficacy assessment at the data cutoff.

Seven of the 14 evaluable patients responded (50%). Three patients (21%) had a complete response (CR), 4 (29%) had a partial response (PR), 3 (21%) had stable disease, and 4 (29%) progressed.

“There were several patients with lengthy responses,” Dr Haverkos noted. “One patient had an ongoing response at 16 months, another at 11 months, and a number of patients had ongoing responses at 7 months.”

All 3 patients with a CR had PTCL NOS and received the 800 mg fasting dose of tenalisib.

Two patients with a PR had PTCL NOS, 1 had AITL, and 1 had SPTCL. The SPTCL patient received the 200 mg dose.

The AITL patient and 1 of the PTCL NOS patients received the 800 mg fasting dose. The other PTCL NOS patient received the 400 mg dose.

Efficacy in CTCL

Most CTCL patients (n=23) had mycosis fungoides, but 5 had Sézary syndrome. The patients’ median age at baseline was 68 (range, 39-84), and 57% are female.

Forty-three percent of patients had relapsed disease at baseline, 57% were refractory, and 46% had stage 3 or 4 disease. Patients had received a median of 6 prior therapies (range, 2-15).

The median duration of treatment with tenalisib was 3.4 months.

Eighteen patients were evaluable for efficacy. Eight patients had progressed prior to the first protocol-defined assessment, and 2 patients had not yet reached their first efficacy assessment.

Eight of the 18 evaluable patients responded (44%), all with PRs. Seven patients (39%) had stable disease, and 3 (17%) progressed.

Four patients were still in response beyond 8 months of follow-up, and 1 patient was still in PR beyond 11 months.

Five patients with a PR had received the 800 mg fasting dose of tenalisib. Two received the 800 mg fed dose, and 1 patient received the drug at 400 mg.

Overall safety

Treatment-related AEs included transaminitis (25%, 14/55), diarrhea (11%, n=6), fatigue (6%, n=11), headache (9%, n=5), rash (9%, n=5), nausea (5%, n=3), vomiting (5%, n=3), pyrexia (5%, n=3), and dizziness (5%, n=3). Dizziness was only observed in CTCL patients.

Treatment-related grade 3 or higher AEs included transaminitis (20%, n=11), rash (5%, n=3), neutropenia (2%, n=1), hypophosphatemia (2%, n=1), international normalized ratio increase (2%, n=1), sepsis (2%, n=1), pyrexia (2%, n=1), and diplopia secondary to neuropathy (2%, n=1).

Seventy-six percent (n=42) of patients discontinued treatment. Sixty-eight percent (n=29) stopped due to progression, 5% (n=2) stopped at investigators’ discretion, 9% (n=4) withdrew consent, 12% (n=5) had a treatment-related AE, and 5% (n=2) had an unrelated AE.

Seventeen PTCL patients stopped treatment due to progression, as did 12 CTCL patients. One patient in each group stopped treatment at investigators’ discretion, and all 4 patients who withdrew consent had CTCL.

Four CTCL patients stopped treatment due to a related AE—transaminitis, sepsis, diarrhea, and diplopia secondary to neuropathy. One PTCL patient stopped treatment due to a related AE, which was transaminitis.

“Tenalisib at the 800 mg fasting dose has demonstrated acceptable safety and tolerability,” Dr Haverkos concluded. “We’ve observed encouraging response rates thus far, which support further evaluation of tenalisib in these patients.”

Photo by Larry Young

LA JOLLA, CA—Fluorodeoxyglucose positron emission tomography (FDG PET) cannot replace bone marrow (BM) biopsy in T-cell lymphomas, according to a speaker at the 10th Annual T-cell Lymphoma Forum.

Researchers found that FDG PET results did not exactly correlate with BM biopsy results relating to tumor involvement in patients with T-cell lymphomas.

However, results from FDG PET were found to be an independent prognostic factor for progression-free survival (PFS) and overall survival (OS).

Youngil Koh, MD, of Seoul National University Hospital in Seoul, South Korea, presented this research in a poster and oral presentation at this year’s T-cell Lymphoma Forum.

He and his colleagues set out to investigate the clinical value of FDG PET for evaluating BM tumor involvement and prognosis in T-cell lymphoma patients.

The team analyzed 109 patients who underwent staging with FDG PET and BM biopsy. Most patients had extranodal natural killer/T-cell lymphoma, nasal type (NKTCL, n=46), or angioimmunoblastic T-cell lymphoma (AITL, n=41).

Patients also had peripheral T-cell lymphoma not otherwise specified (n=12), anaplastic large-cell lymphoma (n=4), enteropathy-associated T-cell lymphoma (n=4), and subcutaneous panniculitis-like T-cell lymphoma (n=2).

Most patients (87.2%) received chemotherapy as first-line treatment. Fifty percent were CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) or CHOP-like regimens, 48.1% were IMEP (ifosphamide, methotrexate, etoposide, and prednisolone) or IMEP-like regimens, and 1.9% were “other” regimens.

Other first-line treatments included radiotherapy followed by chemotherapy (10.1%), excision (0.9%), and no treatment (1.8%).

The patients’ median OS was 60.03 months, and the median PFS was 15.7 months.

BM involvement

The researchers analyzed PET BM uptake both visually and quantitatively using the marrow-to-liver ratio (MLR), and they compared these results to BM biopsy results.

According to BM biopsy, 35.8% of patients had tumor involvement.

By visual analysis, the sensitivity of PET for diagnosing positive BM biopsy was 58.5%, and the specificity was 77.9%. By MLR, the sensitivity was 64.1%, and the specificity was 72.9%.

The diagnostic performance of PET for BM involvement was not different across the lymphoma subtypes, Dr Koh said.

Prognosis

“Although FDG PET did not correlate very well with bone marrow biopsy, it had prognostic value, especially MLR,” Dr Koh noted. “And most importantly, in bone marrow biopsy-negative patients, it [MLR] had prognostic value.”

MLR was a significant prognostic factor for PFS (P=0.005) and OS (P<0.001). The same was true for BM biopsy (P=0.009 for PFS and P<0.001 for OS), while visual PET analysis was a significant prognostic factor for OS (P=0.015) but not PFS (P=0.476).

In patients negative by BM biopsy, MLR was a significant prognostic factor for PFS (P=0.001) and OS (P=0.005).

Dr Koh and his colleagues also analyzed the prognostic value of PET and BM biopsy specifically in patients with NKTCL and AITL.

In AITL patients, BM biopsy was a significant prognostic factor for OS (P=0.002) but not PFS (P=0.246). Visual PET analysis was not significant for PFS (P=0.910) or OS (P=0.581), and neither was MLR (P=0.053 for PFS and P=0.156 for OS).

In patients with NKTCL, BM biopsy was a significant prognostic factor for PFS (P=0.008) and OS (P<0.001). Visual PET analysis was not significant for PFS (P=0.469) or OS (P=0.092). And MLR was significant for PFS (P=0.004) and OS (P=0.012).

“Bone marrow findings of FDG PET are an independent prognostic factor in these tumors,” Dr Koh said, “suggesting the biologic relevance of FDG PET findings for aggressiveness or covert bone marrow involvement of tumor cells.”

Photo by Larry Young

LA JOLLA, CA—Fluorodeoxyglucose positron emission tomography (FDG PET) cannot replace bone marrow (BM) biopsy in T-cell lymphomas, according to a speaker at the 10th Annual T-cell Lymphoma Forum.

Researchers found that FDG PET results did not exactly correlate with BM biopsy results relating to tumor involvement in patients with T-cell lymphomas.

However, results from FDG PET were found to be an independent prognostic factor for progression-free survival (PFS) and overall survival (OS).

Youngil Koh, MD, of Seoul National University Hospital in Seoul, South Korea, presented this research in a poster and oral presentation at this year’s T-cell Lymphoma Forum.

He and his colleagues set out to investigate the clinical value of FDG PET for evaluating BM tumor involvement and prognosis in T-cell lymphoma patients.

The team analyzed 109 patients who underwent staging with FDG PET and BM biopsy. Most patients had extranodal natural killer/T-cell lymphoma, nasal type (NKTCL, n=46), or angioimmunoblastic T-cell lymphoma (AITL, n=41).

Patients also had peripheral T-cell lymphoma not otherwise specified (n=12), anaplastic large-cell lymphoma (n=4), enteropathy-associated T-cell lymphoma (n=4), and subcutaneous panniculitis-like T-cell lymphoma (n=2).

Most patients (87.2%) received chemotherapy as first-line treatment. Fifty percent were CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) or CHOP-like regimens, 48.1% were IMEP (ifosphamide, methotrexate, etoposide, and prednisolone) or IMEP-like regimens, and 1.9% were “other” regimens.

Other first-line treatments included radiotherapy followed by chemotherapy (10.1%), excision (0.9%), and no treatment (1.8%).

The patients’ median OS was 60.03 months, and the median PFS was 15.7 months.

BM involvement

The researchers analyzed PET BM uptake both visually and quantitatively using the marrow-to-liver ratio (MLR), and they compared these results to BM biopsy results.

According to BM biopsy, 35.8% of patients had tumor involvement.

By visual analysis, the sensitivity of PET for diagnosing positive BM biopsy was 58.5%, and the specificity was 77.9%. By MLR, the sensitivity was 64.1%, and the specificity was 72.9%.

The diagnostic performance of PET for BM involvement was not different across the lymphoma subtypes, Dr Koh said.

Prognosis

“Although FDG PET did not correlate very well with bone marrow biopsy, it had prognostic value, especially MLR,” Dr Koh noted. “And most importantly, in bone marrow biopsy-negative patients, it [MLR] had prognostic value.”

MLR was a significant prognostic factor for PFS (P=0.005) and OS (P<0.001). The same was true for BM biopsy (P=0.009 for PFS and P<0.001 for OS), while visual PET analysis was a significant prognostic factor for OS (P=0.015) but not PFS (P=0.476).

In patients negative by BM biopsy, MLR was a significant prognostic factor for PFS (P=0.001) and OS (P=0.005).

Dr Koh and his colleagues also analyzed the prognostic value of PET and BM biopsy specifically in patients with NKTCL and AITL.

In AITL patients, BM biopsy was a significant prognostic factor for OS (P=0.002) but not PFS (P=0.246). Visual PET analysis was not significant for PFS (P=0.910) or OS (P=0.581), and neither was MLR (P=0.053 for PFS and P=0.156 for OS).

In patients with NKTCL, BM biopsy was a significant prognostic factor for PFS (P=0.008) and OS (P<0.001). Visual PET analysis was not significant for PFS (P=0.469) or OS (P=0.092). And MLR was significant for PFS (P=0.004) and OS (P=0.012).

“Bone marrow findings of FDG PET are an independent prognostic factor in these tumors,” Dr Koh said, “suggesting the biologic relevance of FDG PET findings for aggressiveness or covert bone marrow involvement of tumor cells.”

Photo by Larry Young

LA JOLLA, CA—Fluorodeoxyglucose positron emission tomography (FDG PET) cannot replace bone marrow (BM) biopsy in T-cell lymphomas, according to a speaker at the 10th Annual T-cell Lymphoma Forum.

Researchers found that FDG PET results did not exactly correlate with BM biopsy results relating to tumor involvement in patients with T-cell lymphomas.

However, results from FDG PET were found to be an independent prognostic factor for progression-free survival (PFS) and overall survival (OS).

Youngil Koh, MD, of Seoul National University Hospital in Seoul, South Korea, presented this research in a poster and oral presentation at this year’s T-cell Lymphoma Forum.

He and his colleagues set out to investigate the clinical value of FDG PET for evaluating BM tumor involvement and prognosis in T-cell lymphoma patients.

The team analyzed 109 patients who underwent staging with FDG PET and BM biopsy. Most patients had extranodal natural killer/T-cell lymphoma, nasal type (NKTCL, n=46), or angioimmunoblastic T-cell lymphoma (AITL, n=41).

Patients also had peripheral T-cell lymphoma not otherwise specified (n=12), anaplastic large-cell lymphoma (n=4), enteropathy-associated T-cell lymphoma (n=4), and subcutaneous panniculitis-like T-cell lymphoma (n=2).

Most patients (87.2%) received chemotherapy as first-line treatment. Fifty percent were CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) or CHOP-like regimens, 48.1% were IMEP (ifosphamide, methotrexate, etoposide, and prednisolone) or IMEP-like regimens, and 1.9% were “other” regimens.

Other first-line treatments included radiotherapy followed by chemotherapy (10.1%), excision (0.9%), and no treatment (1.8%).

The patients’ median OS was 60.03 months, and the median PFS was 15.7 months.

BM involvement

The researchers analyzed PET BM uptake both visually and quantitatively using the marrow-to-liver ratio (MLR), and they compared these results to BM biopsy results.

According to BM biopsy, 35.8% of patients had tumor involvement.

By visual analysis, the sensitivity of PET for diagnosing positive BM biopsy was 58.5%, and the specificity was 77.9%. By MLR, the sensitivity was 64.1%, and the specificity was 72.9%.

The diagnostic performance of PET for BM involvement was not different across the lymphoma subtypes, Dr Koh said.

Prognosis

“Although FDG PET did not correlate very well with bone marrow biopsy, it had prognostic value, especially MLR,” Dr Koh noted. “And most importantly, in bone marrow biopsy-negative patients, it [MLR] had prognostic value.”

MLR was a significant prognostic factor for PFS (P=0.005) and OS (P<0.001). The same was true for BM biopsy (P=0.009 for PFS and P<0.001 for OS), while visual PET analysis was a significant prognostic factor for OS (P=0.015) but not PFS (P=0.476).

In patients negative by BM biopsy, MLR was a significant prognostic factor for PFS (P=0.001) and OS (P=0.005).

Dr Koh and his colleagues also analyzed the prognostic value of PET and BM biopsy specifically in patients with NKTCL and AITL.

In AITL patients, BM biopsy was a significant prognostic factor for OS (P=0.002) but not PFS (P=0.246). Visual PET analysis was not significant for PFS (P=0.910) or OS (P=0.581), and neither was MLR (P=0.053 for PFS and P=0.156 for OS).

In patients with NKTCL, BM biopsy was a significant prognostic factor for PFS (P=0.008) and OS (P<0.001). Visual PET analysis was not significant for PFS (P=0.469) or OS (P=0.092). And MLR was significant for PFS (P=0.004) and OS (P=0.012).

“Bone marrow findings of FDG PET are an independent prognostic factor in these tumors,” Dr Koh said, “suggesting the biologic relevance of FDG PET findings for aggressiveness or covert bone marrow involvement of tumor cells.”

Photo by Larry Young

LA JOLLA, CA—Results of a phase 1 trial suggest MRG-106 can provide clinical improvement in patients with mycosis fungoides (MF), whether the drug is given alone or in conjunction with other therapies.

MRG-106 is an inhibitor of microRNA-155, which is upregulated in MF.

In this ongoing trial, 90% of patients who received MRG-106 have experienced an improvement in mSWAT score, and 59% of patients who received the drug for at least 1 month had a partial response.

The most common adverse events (AEs) attributed to MRG-106 were neutropenia, injection site pain, and fatigue.

Christiane Querfeld, MD, PhD, of the City of Hope in Duarte, California, presented these results at the 10th Annual T-cell Lymphoma Forum. The research is sponsored by miRagen Therapeutics, Inc., the company developing MRG-106.

The trial has enrolled 36 MF patients, 69% of whom are male. Their median age at enrollment was 63 (range, 21-85).

Patients had received a median of 4 prior systemic therapies (range, 1-13) and a median of 3 prior skin-directed therapies (range, 1-8).

At baseline, patients had a median mSWAT score of 43 (range, 2-180). The modified Severity Weighted Assessment Tool (mSWAT) measures the severity of skin disease over a patient’s body.

Part A

In part A of the study, 6 patients received MRG-106 via intralesional injection. A 75 mg dose of the drug was found to be well-tolerated, producing generally minor injection site reactions.

In addition, intralesional injection of MRG-106 produced improvements in CAILS score. The Composite Assessment of Index Lesion Severity (CAILS) score is obtained by adding the severity score of erythema, scaling, plaque elevation, and surface area for up to 5 index lesions.

Part B

In part B, 30 patients received MRG-106 via subcutaneous (SQ) injection, intravenous (IV) infusion, or IV bolus injection.

Patients who received SQ injection or IV infusion received doses of 300 mg, 600 mg, or 900 mg. Those who received an IV bolus only received the 300 mg dose.

Twenty-nine of the 30 patients in part B were evaluable for efficacy. Twenty-six of these patients—90%—had an improvement in mSWAT score from baseline.

“Twenty-six patients had at least stable disease to partial response,” Dr Querfeld noted. “No complete responses yet, but we’re close.”

Twelve patients were still receiving MRG-106 at last follow-up.

Ten of the 17 patients (59%) who had received MRG-106 for more than 1 month had at least a 50% improvement in mSWAT score, or a partial response. Once this was achieved, responses were durable.

One patient was still in response at roughly 470 days of follow-up.

Concomitant therapies

Dr Querfeld and her colleagues looked at patient outcomes in the context of concomitant therapies as well. They analyzed data from 26 patients who had received at least 6 doses of MRG-106.

Half of these patients were receiving MRG-106 alone, and the other half were receiving concomitant therapies, including bexarotene (n=7), interferon-alfa (n=2), methotrexate (n=1), vorinostat (n=1), and “other” treatments (n=2). Patients had been receiving these therapies for anywhere from 4 months to 45 months.

Outcomes were similar in the monotherapy and combination treatment groups. Seven patients in each group had at least a 50% improvement in mSWAT score.

Dosing and administration

“It appears the infusion is superior to the subcutaneous administration,” Dr Querfeld said.

She noted that durable partial responses have been achieved at all dose levels, but the 300 mg and 600 mg IV infusions had the best efficacy and tolerability profiles.

With the 300 mg IV bolus, fewer patients remained on treatment for more than 1 cycle, as compared to the other dosing cohorts. Dr Querfeld said this may be a result of lower total exposure or tolerability due to higher plasma C_max.

She also noted that patients who received MRG-106 SQ at 600 mg or higher had a higher incidence of injection site reactions.

Safety

AEs of any grade that were attributed to MRG-106 include neutropenia (16%), injection site pain (16%), fatigue (14%), nausea (5%), pruritus (5%), and headache (5%).

Grade 3/4 AEs attributed to MRG-106 were neutropenia (5%) and pruritus (5%).

There were no serious AEs attributed to MRG-106, but there were 2 dose-limiting toxicities. One was a grade 3 tumor flare in a patient receiving the 300 mg IV bolus.

The other dose-limiting toxicity was grade 3 worsening pruritus and possible tumor flare, which occurred twice in 1 patient—with the 900 mg SQ dose and with the 300 mg IV infusion.

The 300 mg IV infusion is the anticipated phase 2 dose.

Photo by Larry Young

LA JOLLA, CA—Results of a phase 1 trial suggest MRG-106 can provide clinical improvement in patients with mycosis fungoides (MF), whether the drug is given alone or in conjunction with other therapies.

MRG-106 is an inhibitor of microRNA-155, which is upregulated in MF.

In this ongoing trial, 90% of patients who received MRG-106 have experienced an improvement in mSWAT score, and 59% of patients who received the drug for at least 1 month had a partial response.

The most common adverse events (AEs) attributed to MRG-106 were neutropenia, injection site pain, and fatigue.

Christiane Querfeld, MD, PhD, of the City of Hope in Duarte, California, presented these results at the 10th Annual T-cell Lymphoma Forum. The research is sponsored by miRagen Therapeutics, Inc., the company developing MRG-106.

The trial has enrolled 36 MF patients, 69% of whom are male. Their median age at enrollment was 63 (range, 21-85).

Patients had received a median of 4 prior systemic therapies (range, 1-13) and a median of 3 prior skin-directed therapies (range, 1-8).

At baseline, patients had a median mSWAT score of 43 (range, 2-180). The modified Severity Weighted Assessment Tool (mSWAT) measures the severity of skin disease over a patient’s body.

Part A

In part A of the study, 6 patients received MRG-106 via intralesional injection. A 75 mg dose of the drug was found to be well-tolerated, producing generally minor injection site reactions.

In addition, intralesional injection of MRG-106 produced improvements in CAILS score. The Composite Assessment of Index Lesion Severity (CAILS) score is obtained by adding the severity score of erythema, scaling, plaque elevation, and surface area for up to 5 index lesions.

Part B

In part B, 30 patients received MRG-106 via subcutaneous (SQ) injection, intravenous (IV) infusion, or IV bolus injection.

Patients who received SQ injection or IV infusion received doses of 300 mg, 600 mg, or 900 mg. Those who received an IV bolus only received the 300 mg dose.

Twenty-nine of the 30 patients in part B were evaluable for efficacy. Twenty-six of these patients—90%—had an improvement in mSWAT score from baseline.

“Twenty-six patients had at least stable disease to partial response,” Dr Querfeld noted. “No complete responses yet, but we’re close.”

Twelve patients were still receiving MRG-106 at last follow-up.

Ten of the 17 patients (59%) who had received MRG-106 for more than 1 month had at least a 50% improvement in mSWAT score, or a partial response. Once this was achieved, responses were durable.

One patient was still in response at roughly 470 days of follow-up.

Concomitant therapies

Dr Querfeld and her colleagues looked at patient outcomes in the context of concomitant therapies as well. They analyzed data from 26 patients who had received at least 6 doses of MRG-106.

Half of these patients were receiving MRG-106 alone, and the other half were receiving concomitant therapies, including bexarotene (n=7), interferon-alfa (n=2), methotrexate (n=1), vorinostat (n=1), and “other” treatments (n=2). Patients had been receiving these therapies for anywhere from 4 months to 45 months.

Outcomes were similar in the monotherapy and combination treatment groups. Seven patients in each group had at least a 50% improvement in mSWAT score.

Dosing and administration

“It appears the infusion is superior to the subcutaneous administration,” Dr Querfeld said.

She noted that durable partial responses have been achieved at all dose levels, but the 300 mg and 600 mg IV infusions had the best efficacy and tolerability profiles.

With the 300 mg IV bolus, fewer patients remained on treatment for more than 1 cycle, as compared to the other dosing cohorts. Dr Querfeld said this may be a result of lower total exposure or tolerability due to higher plasma C_max.

She also noted that patients who received MRG-106 SQ at 600 mg or higher had a higher incidence of injection site reactions.

Safety

AEs of any grade that were attributed to MRG-106 include neutropenia (16%), injection site pain (16%), fatigue (14%), nausea (5%), pruritus (5%), and headache (5%).

Grade 3/4 AEs attributed to MRG-106 were neutropenia (5%) and pruritus (5%).

There were no serious AEs attributed to MRG-106, but there were 2 dose-limiting toxicities. One was a grade 3 tumor flare in a patient receiving the 300 mg IV bolus.

The other dose-limiting toxicity was grade 3 worsening pruritus and possible tumor flare, which occurred twice in 1 patient—with the 900 mg SQ dose and with the 300 mg IV infusion.

The 300 mg IV infusion is the anticipated phase 2 dose.

Photo by Larry Young

LA JOLLA, CA—Results of a phase 1 trial suggest MRG-106 can provide clinical improvement in patients with mycosis fungoides (MF), whether the drug is given alone or in conjunction with other therapies.

MRG-106 is an inhibitor of microRNA-155, which is upregulated in MF.

In this ongoing trial, 90% of patients who received MRG-106 have experienced an improvement in mSWAT score, and 59% of patients who received the drug for at least 1 month had a partial response.

The most common adverse events (AEs) attributed to MRG-106 were neutropenia, injection site pain, and fatigue.

Christiane Querfeld, MD, PhD, of the City of Hope in Duarte, California, presented these results at the 10th Annual T-cell Lymphoma Forum. The research is sponsored by miRagen Therapeutics, Inc., the company developing MRG-106.

The trial has enrolled 36 MF patients, 69% of whom are male. Their median age at enrollment was 63 (range, 21-85).

Patients had received a median of 4 prior systemic therapies (range, 1-13) and a median of 3 prior skin-directed therapies (range, 1-8).

At baseline, patients had a median mSWAT score of 43 (range, 2-180). The modified Severity Weighted Assessment Tool (mSWAT) measures the severity of skin disease over a patient’s body.

Part A

In part A of the study, 6 patients received MRG-106 via intralesional injection. A 75 mg dose of the drug was found to be well-tolerated, producing generally minor injection site reactions.

In addition, intralesional injection of MRG-106 produced improvements in CAILS score. The Composite Assessment of Index Lesion Severity (CAILS) score is obtained by adding the severity score of erythema, scaling, plaque elevation, and surface area for up to 5 index lesions.

Part B

In part B, 30 patients received MRG-106 via subcutaneous (SQ) injection, intravenous (IV) infusion, or IV bolus injection.

Patients who received SQ injection or IV infusion received doses of 300 mg, 600 mg, or 900 mg. Those who received an IV bolus only received the 300 mg dose.

Twenty-nine of the 30 patients in part B were evaluable for efficacy. Twenty-six of these patients—90%—had an improvement in mSWAT score from baseline.

“Twenty-six patients had at least stable disease to partial response,” Dr Querfeld noted. “No complete responses yet, but we’re close.”

Twelve patients were still receiving MRG-106 at last follow-up.

Ten of the 17 patients (59%) who had received MRG-106 for more than 1 month had at least a 50% improvement in mSWAT score, or a partial response. Once this was achieved, responses were durable.

One patient was still in response at roughly 470 days of follow-up.

Concomitant therapies

Dr Querfeld and her colleagues looked at patient outcomes in the context of concomitant therapies as well. They analyzed data from 26 patients who had received at least 6 doses of MRG-106.

Half of these patients were receiving MRG-106 alone, and the other half were receiving concomitant therapies, including bexarotene (n=7), interferon-alfa (n=2), methotrexate (n=1), vorinostat (n=1), and “other” treatments (n=2). Patients had been receiving these therapies for anywhere from 4 months to 45 months.

Outcomes were similar in the monotherapy and combination treatment groups. Seven patients in each group had at least a 50% improvement in mSWAT score.

Dosing and administration

“It appears the infusion is superior to the subcutaneous administration,” Dr Querfeld said.

She noted that durable partial responses have been achieved at all dose levels, but the 300 mg and 600 mg IV infusions had the best efficacy and tolerability profiles.

With the 300 mg IV bolus, fewer patients remained on treatment for more than 1 cycle, as compared to the other dosing cohorts. Dr Querfeld said this may be a result of lower total exposure or tolerability due to higher plasma C_max.

She also noted that patients who received MRG-106 SQ at 600 mg or higher had a higher incidence of injection site reactions.

Safety

AEs of any grade that were attributed to MRG-106 include neutropenia (16%), injection site pain (16%), fatigue (14%), nausea (5%), pruritus (5%), and headache (5%).

Grade 3/4 AEs attributed to MRG-106 were neutropenia (5%) and pruritus (5%).

There were no serious AEs attributed to MRG-106, but there were 2 dose-limiting toxicities. One was a grade 3 tumor flare in a patient receiving the 300 mg IV bolus.

The other dose-limiting toxicity was grade 3 worsening pruritus and possible tumor flare, which occurred twice in 1 patient—with the 900 mg SQ dose and with the 300 mg IV infusion.

The 300 mg IV infusion is the anticipated phase 2 dose.

LA JOLLA, CALIF. – The words “rapid approval” and “Food and Drug Administration” rarely appear in the same sentence. But despite that perception, the pace of hematologic drug development has been accelerating over the last several years, according to an agency staffer.

“FDA is committed toward the expedited development of safe and effective therapies for serious and life-threatening diseases,” R. Angelo de Claro, MD, of the FDA’s Office of Hematology and Oncology Products said at the annual T-cell Lymphoma Forum. Dr. de Claro outlined his agency’s efforts to accelerate approval of drugs for treatment of T-cell malignancies.
 

Hematologic drug bonanza

In 2017 alone, the FDA approved 17 agents for new or expanded indications for hematologic malignancies, including brentuximab vedotin (Adcetris) for anaplastic large cell lymphoma (ALCL) and CD30-positive mycosis fungoides (MF).

Approval was based on a 56% objective response rate for brentuximab vedotin versus 12% for physician’s choice in a phase 3 trial (ALCANZA) of 131 patients with mycosis fungoides or primary cutaneous ALCL. All patients had received one prior systemic therapy and were randomized (1:1) to receive either brentuximab vedotin or the physician’s choice of methotrexate or bexarotene.

Dr. de Claro noted that in the ALCANZA trial, patients were required to have one or more biopsy samples with at least 10% CD30 expression, but among 184 patients with MF screened for the trial, 32% were ineligible because of less than 10% CD30 expression. The FDA therefore requested additional efficacy data for patients with MF with less than 10% CD30 expression and accepted data from two investigator-sponsored trials showing that 35 patients with MF expressing CD30 on 1%-9% of cells had a 31% overall response rate, whereas two patients with no CD30 expression did not have responses.

Who minds the store

Hematology products are under the aegis of the FDA’s Oncology Center of Excellence. Oversight includes benign hematology products, as well as products for hematologic cancers and hematologic support. Hematology and oncology toxicology is monitored by pharmacologists and toxicologists in a separate division, he explained.

“The Oncology Center of Excellence was formally launched in 2017 as part of the 21st century CURES Act. The mission of the Oncology Center of Excellence is to achieve patient-centered regulatory decision making through innovation and collaboration,” he said.

Getting the nod

To get approved, a new therapy requires “substantial” evidence of efficacy and safety. Regular approvals are based on either direct measures of clinical benefits – how a patient “feels, functions, or survives” – or a measure of the effect of a drug on an established surrogate endpoint.

For an accelerated approval, developers must be able to show evidence on either a surrogate or intermediate clinical endpoint that the agent is reasonably likely to offer a benefit and be a meaningful improvement over available therapies. Postapproval trials may be needed to verify the proposed benefits.

FDA accelerated approval programs include:

• Fast track. The pathway requires nonclinical or clinical data demonstrating the potential for addressing an unmet need.
• Breakthrough therapy. This pathway requires preliminary clinical evidence demonstrating substantial improvement over existing available therapies.
• Priority review. These are agents that, if approved, would provide significant improvements in safety or effectiveness.
• Accelerated approval. The drug must demonstrate an effect on an “endpoint reasonably likely to predict clinical benefit over available therapies.”

Dr. de Claro is employed by the FDA. The T-Cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization.

hematologynews@frontlinemedcom.com
 

LA JOLLA, CALIF. – The words “rapid approval” and “Food and Drug Administration” rarely appear in the same sentence. But despite that perception, the pace of hematologic drug development has been accelerating over the last several years, according to an agency staffer.

“FDA is committed toward the expedited development of safe and effective therapies for serious and life-threatening diseases,” R. Angelo de Claro, MD, of the FDA’s Office of Hematology and Oncology Products said at the annual T-cell Lymphoma Forum. Dr. de Claro outlined his agency’s efforts to accelerate approval of drugs for treatment of T-cell malignancies.
 

Hematologic drug bonanza

In 2017 alone, the FDA approved 17 agents for new or expanded indications for hematologic malignancies, including brentuximab vedotin (Adcetris) for anaplastic large cell lymphoma (ALCL) and CD30-positive mycosis fungoides (MF).

Approval was based on a 56% objective response rate for brentuximab vedotin versus 12% for physician’s choice in a phase 3 trial (ALCANZA) of 131 patients with mycosis fungoides or primary cutaneous ALCL. All patients had received one prior systemic therapy and were randomized (1:1) to receive either brentuximab vedotin or the physician’s choice of methotrexate or bexarotene.

Dr. de Claro noted that in the ALCANZA trial, patients were required to have one or more biopsy samples with at least 10% CD30 expression, but among 184 patients with MF screened for the trial, 32% were ineligible because of less than 10% CD30 expression. The FDA therefore requested additional efficacy data for patients with MF with less than 10% CD30 expression and accepted data from two investigator-sponsored trials showing that 35 patients with MF expressing CD30 on 1%-9% of cells had a 31% overall response rate, whereas two patients with no CD30 expression did not have responses.

Who minds the store

Hematology products are under the aegis of the FDA’s Oncology Center of Excellence. Oversight includes benign hematology products, as well as products for hematologic cancers and hematologic support. Hematology and oncology toxicology is monitored by pharmacologists and toxicologists in a separate division, he explained.

“The Oncology Center of Excellence was formally launched in 2017 as part of the 21st century CURES Act. The mission of the Oncology Center of Excellence is to achieve patient-centered regulatory decision making through innovation and collaboration,” he said.

Getting the nod

To get approved, a new therapy requires “substantial” evidence of efficacy and safety. Regular approvals are based on either direct measures of clinical benefits – how a patient “feels, functions, or survives” – or a measure of the effect of a drug on an established surrogate endpoint.

For an accelerated approval, developers must be able to show evidence on either a surrogate or intermediate clinical endpoint that the agent is reasonably likely to offer a benefit and be a meaningful improvement over available therapies. Postapproval trials may be needed to verify the proposed benefits.

FDA accelerated approval programs include:

• Fast track. The pathway requires nonclinical or clinical data demonstrating the potential for addressing an unmet need.
• Breakthrough therapy. This pathway requires preliminary clinical evidence demonstrating substantial improvement over existing available therapies.
• Priority review. These are agents that, if approved, would provide significant improvements in safety or effectiveness.
• Accelerated approval. The drug must demonstrate an effect on an “endpoint reasonably likely to predict clinical benefit over available therapies.”

Dr. de Claro is employed by the FDA. The T-Cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization.

hematologynews@frontlinemedcom.com
 

LA JOLLA, CALIF. – The words “rapid approval” and “Food and Drug Administration” rarely appear in the same sentence. But despite that perception, the pace of hematologic drug development has been accelerating over the last several years, according to an agency staffer.

“FDA is committed toward the expedited development of safe and effective therapies for serious and life-threatening diseases,” R. Angelo de Claro, MD, of the FDA’s Office of Hematology and Oncology Products said at the annual T-cell Lymphoma Forum. Dr. de Claro outlined his agency’s efforts to accelerate approval of drugs for treatment of T-cell malignancies.
 

Hematologic drug bonanza

In 2017 alone, the FDA approved 17 agents for new or expanded indications for hematologic malignancies, including brentuximab vedotin (Adcetris) for anaplastic large cell lymphoma (ALCL) and CD30-positive mycosis fungoides (MF).

Approval was based on a 56% objective response rate for brentuximab vedotin versus 12% for physician’s choice in a phase 3 trial (ALCANZA) of 131 patients with mycosis fungoides or primary cutaneous ALCL. All patients had received one prior systemic therapy and were randomized (1:1) to receive either brentuximab vedotin or the physician’s choice of methotrexate or bexarotene.

Dr. de Claro noted that in the ALCANZA trial, patients were required to have one or more biopsy samples with at least 10% CD30 expression, but among 184 patients with MF screened for the trial, 32% were ineligible because of less than 10% CD30 expression. The FDA therefore requested additional efficacy data for patients with MF with less than 10% CD30 expression and accepted data from two investigator-sponsored trials showing that 35 patients with MF expressing CD30 on 1%-9% of cells had a 31% overall response rate, whereas two patients with no CD30 expression did not have responses.

Who minds the store

Hematology products are under the aegis of the FDA’s Oncology Center of Excellence. Oversight includes benign hematology products, as well as products for hematologic cancers and hematologic support. Hematology and oncology toxicology is monitored by pharmacologists and toxicologists in a separate division, he explained.

“The Oncology Center of Excellence was formally launched in 2017 as part of the 21st century CURES Act. The mission of the Oncology Center of Excellence is to achieve patient-centered regulatory decision making through innovation and collaboration,” he said.

Getting the nod

To get approved, a new therapy requires “substantial” evidence of efficacy and safety. Regular approvals are based on either direct measures of clinical benefits – how a patient “feels, functions, or survives” – or a measure of the effect of a drug on an established surrogate endpoint.

For an accelerated approval, developers must be able to show evidence on either a surrogate or intermediate clinical endpoint that the agent is reasonably likely to offer a benefit and be a meaningful improvement over available therapies. Postapproval trials may be needed to verify the proposed benefits.

FDA accelerated approval programs include:

• Fast track. The pathway requires nonclinical or clinical data demonstrating the potential for addressing an unmet need.
• Breakthrough therapy. This pathway requires preliminary clinical evidence demonstrating substantial improvement over existing available therapies.
• Priority review. These are agents that, if approved, would provide significant improvements in safety or effectiveness.
• Accelerated approval. The drug must demonstrate an effect on an “endpoint reasonably likely to predict clinical benefit over available therapies.”

Dr. de Claro is employed by the FDA. The T-Cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization.

hematologynews@frontlinemedcom.com